Epidemiologic profile of hemoglobinopathies in Benin.

BACKGROUND: Sickle cell disease is the most common inherited blood disorder in the world with the birth of approximately 300,000 newborns screened each year. In 2009, the World Health Organization ranked the fight against sickle cell disease among the priorities for the Africa regions. The best way to prevent this incurable disease remains, on one hand systematic screening at birth, and on the other the proscription of risky union between heterozygous subjects. AIM: The aim of this study was to analyze the epidemiological profile of sickle cell disease and other hemoglobinopathies in Benin and determine more up-to-date prevalence rates of the disease within the population. METHODS: The hemoglobin profiles of 2910 study participants were determined by quantitative electrophoresis. Samples with abnormal hemoglobin results were subjected to a complete blood count. RESULTS: Our study population was balanced between males (1528) and females (1382) with a sex ratio of 1.1. The mean age ranged from eight years in the pediatric group to 26 years in adults. The hemoglobin electrophoresis profiles found were as follows: 59.7 % Hb AA (normal), 21.7 % Hb AS, 10.2 % Hb AC, 3.1 % Hb SS, 3.7 % Hb SC, and 1.6 % of the rare phenotypes (Hb AD, Hb AE, Hb AF, Hb A/ß-thal, Hb SD, Hb SF, Hb CC and Hb C/ß-thal). Participants with abnormal hemoglobin presented a normochromic normocytic anemia. A total of 356 (12 %) people knew their profile compared to 2554 (88 %) who did not. CONCLUSION: The high prevalence of hemoglobinopathies found in this study highlights in importance of screening in the Benin population.

Disease knowledge and health literacy in parents of children with sickle cell disease.

We aimed to (1) describe sickle cell disease (SCD) knowledge and health literacy levels in parents of children with SCD, (2) examine associations with socio-demographic factors and (3) analyse the association with hospital admissions and frequency of occurrence of painful episodes. Parents who presented with their child at routine hospital consultation at the National Sickle Cell Disease Centre in Benin were administered a questionnaire assessing SCD knowledge, health literacy (newest vital sign [NVS]) and socio-demographic and clinical characteristics. In total, 117 parents participated (108, 92.3% females). The predominant SCD genotype was HbSS (79.5%). The average SCD knowledge score was 13.6 (standard deviation [SD] = 2.0). Only 34 (29.1%) participants correctly answered ≥70% of the questions, indicating good knowledge. Health literacy was relatively low (mean NVS score = 3.3; SD = 1.1). SCD knowledge was higher in parents with older children (p = 0.001) and higher education levels (primary, p = 0.010; tertiary, p = 0.036 compared to participants with no formal education). Hospital admissions were more frequent when parents had lower SCD knowledge (p = 0.034) and in parents with younger children (p = 0.039). No associations were found between health literacy and hospital admissions (p = 0.940) and frequency of occurrence of painful episodes (p = 0.224). Continuous disease-specific education for parents of children with SCD may help them better identify and prevent the occurrence of symptoms and decrease the number of hospital admissions.

Comparative Analysis of Iron Homeostasis in Sub-Saharan African Children with Sickle Cell Disease and Their Unaffected Siblings.

Iron is an essential trace element subject to tight regulation to ensure adequate running of biological processes. In sub-Saharan Africa where hemoglobinopathies are common, iron homeostasis is likely to be impaired by these conditions. Here, we assessed and compared key serum proteins associated with iron metabolism between sub-Saharan African children with sickle cell disease (SCD) and their unaffected siblings. Complete blood counts and serum concentrations of four key proteins involved in iron regulation (ferritin, transferrin, sTfR, and hepcidin) were measured for 73 children with SCD and 68 healthy siblings in Benin, West Africa. We found significant differences in concentration of transferrin, sTfR, and ferritin between the two groups. Hepcidin concentrations were found at unusually high concentrations but did not differ among the two groups. We found a significant negative correlation between hepcidin levels and both MCH and MCV in the SCD group and report that sTfR concentrations show a correlation with MCV and MHC in opposite directions in the two groups. These results highlight the unusually high levels of hepcidin in the Beninese population and the patterns of differential iron homeostasis taking place under SCD status. These results lay the foundation for a systematic evaluation of the underlying mechanisms deregulating iron homeostasis in populations with SCD or high prevalence of iron deficiency.

Genomic architecture of sickle cell disease in West African children.

Sickle cell disease (SCD) is a congenital blood disease, affecting predominantly children from sub-Saharan Africa, but also populations world-wide. Although the causal mutation of SCD is known, the sources of clinical variability of SCD remain poorly understood, with only a few highly heritable traits associated with SCD having been identified. Phenotypic heterogeneity in the clinical expression of SCD is problematic for follow-up (FU), management, and treatment of patients. Here we used the joint analysis of gene expression and whole genome genotyping data to identify the genetic regulatory effects contributing to gene expression variation among groups of patients exhibiting clinical variability, as well as unaffected siblings, in Benin, West Africa. We characterized and replicated patterns of whole blood gene expression variation within and between SCD patients at entry to clinic, as well as in follow-up programs. We present a global map of genes involved in the disease through analysis of whole blood sampled from the cohort. Genome-wide association mapping of gene expression revealed 390 peak genome-wide significant expression SNPs (eSNPs) and 6 significant eSNP-by-clinical status interaction effects. The strong modulation of the transcriptome implicates pathways affecting core circulating cell functions and shows how genotypic regulatory variation likely contributes to the clinical variation observed in SCD.

Evidence for additive and interaction effects of host genotype and infection in malaria.

The host mechanisms responsible for protection against malaria remain poorly understood, with only a few protective genetic effects mapped in humans. Here, we characterize a host-specific genome-wide signature in whole-blood transcriptomes of Plasmodium falciparum-infected West African children and report a demonstration of genotype-by-infection interactions in vivo. Several associations involve transcripts sensitive to infection and implicate complement system, antigen processing and presentation, and T-cell activation (i.e., SLC39A8, C3AR1, FCGR3B, RAD21, RETN, LRRC25, SLC3A2, and TAPBP), including one association that validated a genome-wide association candidate gene (SCO1), implicating binding variation within a noncoding regulatory element. Gene expression profiles in mice infected with Plasmodium chabaudi revealed and validated similar responses and highlighted specific pathways and genes that are likely important responders in both hosts. These results suggest that host variation and its interplay with infection affect children's ability to cope with infection and suggest a polygenic model mounted at the transcriptional level for susceptibility.